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Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)

Primary Purpose

Medium-chain Acyl-CoA Dehydrogenase Deficiency

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sodium phenylbutyrate
Sponsored by
Jerry Vockley, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Medium-chain Acyl-CoA Dehydrogenase Deficiency focused on measuring Medium Chain Acyl-CoA Dehydrogenase Deficiency

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: A diagnosis of MCADD and molecular confirmation of at least one copy of the common c.985A>G mutation. ≥16 years of age for cohort 1 and ≥10-15 years of age for cohort 2. Able to perform and comply with study activities including overnight admission to the PCTRC, placement of an IV catheter, and all blood draws. Negative pregnancy test for all female subjects of childbearing age. Signed informed consent by the subject or parent/guardian of minors. All females of childbearing age and all sexually active males must agree to use an acceptable method of contraception throughout the study. Appropriate contraceptive methods include hormonal contraceptives (oral, injected, implanted, or transdermal), tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier methods. Abstinence is an acceptable form of birth control, though appropriate contraception must be used if the subject becomes sexually active. Exclusion Criteria: Use of any investigational drug within 30 days of Day 1. Active infection (viral or bacterial) or any other intercurrent condition as reported by the subject or noted on physical exam at screening. Any clinical or laboratory abnormality of Grade 3 or greater severity according to the CTCAE v5.0, or Grade 3 elevations in liver enzymes, defined as levels 5-20 times ULN in alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT), or gamma glutamyl transpeptidase (GGT) in a clinically stable subject. Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at increased risk by participating in this study. Use of any medication known to significantly affect renal clearance (e.g., probenecid) or to increase protein catabolism (e.g., corticosteroids), or other medication known to increase ammonia levels (e.g., valproic acid or haloperidol), within the 48 hours prior to Day 1 and throughout the study. Subjects with renal insufficiency will be excluded from the study. Cutoff eGFR <60 mL/min/1.73m2 (GFR categories G3a-G5) will be used as measure of renal insufficiency. Use of sodium benzoate within one week of Day 1. Known hypersensitivity to PAA or PBA. Breastfeeding or lactating females. Subjects at risk of hypokalemia due to pre-existing diagnosis or on medications that can cause hypokalemia. Subjects with type 1 or type 2 diabetes, or who take medications as part of their routine care that can cause hypoglycemia

Sites / Locations

  • UPMC Children's Hospital of PittsburghRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

3.0 g/m2/day QD sodium phenylbutyrate

3.0 g/m2/day BID sodium phenylbutyrate

4.0 g/m2/day BID sodium phenylbutyrate

Arm Description

Up to 8 subjects (4 - ages 10-15 years old and 4 - 16 years of age and older) will be randomized to take 3.0 g/m2/day in one daily dose

Up to 8 subjects (4 - ages 10-15 years old and 4 - 16 years of age and older) will be randomized to take 3.0 g/m2/day divided into two daily doses taken 12 hours apart

Up to 8 subjects (4 - ages 10-15 years old and 4 - 16 years of age and older) will be randomized to take 4.0 g/m2/day divided into two daily doses taken 12 hours apart

Outcomes

Primary Outcome Measures

Number of participants with treatment related adverse events as assessed by CTCAE v5.0

Secondary Outcome Measures

Length of fast before hypoglycemia develops
Comparision of the length of time each subject can fast, comparing their baseline fast to the fast after they are on sodium phenylbutyrate for 4 weeks

Full Information

First Posted
September 28, 2023
Last Updated
October 4, 2023
Sponsor
Jerry Vockley, MD, PhD
Collaborators
Acer Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT06069375
Brief Title
Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
Official Title
A Phase 2, Open-Label, Fixed Dose Study to Evaluate the Use of Sodium Phenylbutyrate (ACER-001) in the Treatment of Pediatric and Adult Patients With MCAD Deficiency Caused by the Common ACADM c.985 A>G (K304E) Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 2023 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jerry Vockley, MD, PhD
Collaborators
Acer Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a medical research study to test a medication in patients 10 years of age and older with a disease called medium-chain acyl-CoA dehydrogenase deficiency (MCADD) caused by the common ACADM c.985 A>G (K304E) mutation. The medication is sodium phenylbutyrate (ACER-001), which is currently FDA approved for the treatment of Urea Cyle Disorders. Previous research suggests that sodium phenylbutyrate may also be effective in the treatment MCADD. This study will investigate the safety and efficacy (how well it works) of sodium phenylbutyrate in patients with MCADD.
Detailed Description
Participation in the study will require two overnight admissions and one outpatient visit at the Clinical and Translational Research Center at the UPMC Children's Hospital of Pittsburgh (also called the PCTRC). The total length of the study is 7 weeks. Subjects will have blood work and an intravenous access line (IV) placed for several blood draws during the overnight visits. Subjects will begin fasting during the admission, which means they may consume only non-caloric fluids (water, unsweetened black coffee or tea, or sugar-free beverages). Bloodwork will be collected during the fast. Following the completion of the fast, the subject will eat a meal and will receive the study drug, sodium phenylbutyrate. The total time of fasting will be up to 24 hours for patients 16 years of age and older and up to 18 hours for patients 10-15 years of age. Dosing for this study will be assigned to one of three doses: 3.0 g/m2/day in one daily dose, 3.0 g/m2/day divided into two daily doses 12 hours apart, and 4.0 g/m2/day divided into two daily doses 12 hours apart. Subjects will return after 4 weeks to undergo the overnight admission and 18/24-hour fasting procedures outlined above. After the Week 5 admission they will no longer take the sodium phenylbutyrate. Subjects will return after 2 weeks for an outpatient visit to have some additional blood work done and to make sure they are not experiencing any adverse effects. All study procedures will be done at no cost to the subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medium-chain Acyl-CoA Dehydrogenase Deficiency
Keywords
Medium Chain Acyl-CoA Dehydrogenase Deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
3.0 g/m2/day QD sodium phenylbutyrate
Arm Type
Experimental
Arm Description
Up to 8 subjects (4 - ages 10-15 years old and 4 - 16 years of age and older) will be randomized to take 3.0 g/m2/day in one daily dose
Arm Title
3.0 g/m2/day BID sodium phenylbutyrate
Arm Type
Experimental
Arm Description
Up to 8 subjects (4 - ages 10-15 years old and 4 - 16 years of age and older) will be randomized to take 3.0 g/m2/day divided into two daily doses taken 12 hours apart
Arm Title
4.0 g/m2/day BID sodium phenylbutyrate
Arm Type
Experimental
Arm Description
Up to 8 subjects (4 - ages 10-15 years old and 4 - 16 years of age and older) will be randomized to take 4.0 g/m2/day divided into two daily doses taken 12 hours apart
Intervention Type
Drug
Intervention Name(s)
Sodium phenylbutyrate
Other Intervention Name(s)
Olpruva
Intervention Description
Open-label design with doses of sodium phenylbutyrate up to 4.0 g/m2/day
Primary Outcome Measure Information:
Title
Number of participants with treatment related adverse events as assessed by CTCAE v5.0
Time Frame
7 weeks
Secondary Outcome Measure Information:
Title
Length of fast before hypoglycemia develops
Description
Comparision of the length of time each subject can fast, comparing their baseline fast to the fast after they are on sodium phenylbutyrate for 4 weeks
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A diagnosis of MCADD and molecular confirmation of at least one copy of the common c.985A>G mutation. ≥16 years of age for cohort 1 and ≥10-15 years of age for cohort 2. Able to perform and comply with study activities including overnight admission to the PCTRC, placement of an IV catheter, and all blood draws. Negative pregnancy test for all female subjects of childbearing age. Signed informed consent by the subject or parent/guardian of minors. All females of childbearing age and all sexually active males must agree to use an acceptable method of contraception throughout the study. Appropriate contraceptive methods include hormonal contraceptives (oral, injected, implanted, or transdermal), tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier methods. Abstinence is an acceptable form of birth control, though appropriate contraception must be used if the subject becomes sexually active. Exclusion Criteria: Use of any investigational drug within 30 days of Day 1. Active infection (viral or bacterial) or any other intercurrent condition as reported by the subject or noted on physical exam at screening. Any clinical or laboratory abnormality of Grade 3 or greater severity according to the CTCAE v5.0, or Grade 3 elevations in liver enzymes, defined as levels 5-20 times ULN in alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT), or gamma glutamyl transpeptidase (GGT) in a clinically stable subject. Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at increased risk by participating in this study. Use of any medication known to significantly affect renal clearance (e.g., probenecid) or to increase protein catabolism (e.g., corticosteroids), or other medication known to increase ammonia levels (e.g., valproic acid or haloperidol), within the 48 hours prior to Day 1 and throughout the study. Subjects with renal insufficiency will be excluded from the study. Cutoff eGFR <60 mL/min/1.73m2 (GFR categories G3a-G5) will be used as measure of renal insufficiency. Use of sodium benzoate within one week of Day 1. Known hypersensitivity to PAA or PBA. Breastfeeding or lactating females. Subjects at risk of hypokalemia due to pre-existing diagnosis or on medications that can cause hypokalemia. Subjects with type 1 or type 2 diabetes, or who take medications as part of their routine care that can cause hypoglycemia
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elizabeth McCracken, MS, CGC
Phone
412-692-5662
Email
elizabeth.mccracken@chp.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerard L Vockley, MD, PhD
Organizational Affiliation
UPMC Children's Hospital of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
UPMC Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth McCracken, MS, CGC
Phone
412-692-5662
Email
elizabeth.mccracken@chp.edu
First Name & Middle Initial & Last Name & Degree
Gerard Vockley, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)

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